Annexin-1 modulates T-cell activation and differentiation

Author:

D'Acquisto Fulvio1,Merghani Ahmed1,Lecona Emilio1,Rosignoli Guglielmo1,Raza Karim2,Buckley Christopher D.2,Flower Roderick J.1,Perretti Mauro1

Affiliation:

1. William Harvey Research Institute, Bart's and The London, Queen Mary School of Medicine and Dentistry, Charterhouse Square, London, United Kingdom;

2. Division of Immunity and Infection, MRC Centre for Immune Regulation, University of Birmingham, Edgbaston, United Kingdom

Abstract

Abstract Annexin-1 is an anti-inflammatory protein that plays an important homeostatic role in innate immunity; however, its potential actions in the modulation of adaptive immunity have never been explored. Although inactive by itself, addition of annexin-1 to stimulated T cells augmented anti-CD3/CD28-mediated CD25 and CD69 expression and cell proliferation. This effect was paralleled by increased nuclear factor-κB (NF-κB), nuclear factor of activated T cells (NFATs), and activator protein-1 (AP-1) activation and preceded by a rapid T-cell receptor (TCR)–induced externalization of the annexin-1 receptor. Interestingly, differentiation of naive T cells in the presence of annexin-1 increased skewing in Th1 cells; in the collagen-induced arthritis model, treatment of mice with annexin-1 during the immunization phase exacerbated signs and symptoms at disease onset. Consistent with these findings, blood CD4+ cells from patients with rheumatoid arthritis showed a marked up-regulation of annexin-1 expression. Together these results demonstrate that annexin-1 is a molecular “tuner” of TCR signaling and suggest this protein might represent a new target for the development of drugs directed to pathologies where an unbalanced Th1/Th2 response or an aberrant activation of T cells is the major etiologic factor.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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